Zirconium hexafluorogermanate (zr(gef6)2) and zirconyl hexafluorogermanate (zrogef6)



United States Patent U.S. CI. 2351 3 Claims ABSTRACT OF THE DISCLOSURENew compositions of matter, namely, zirconium hexafiuorogermanate[Zr(G6F and zirconyl hexafluorogermanate [ZrOGeF have been discovered.These compounds, when incorporated in oral compositions for dentalcaries prophylaxis (e.g., as constituents of a dentifrice, prophylaxispaste, or mouthwash), have demonstrated substantial utility asanticariogenic agents.

This invention relates to new compositions of matter, and moreparticularly to salts comprising zirconium, germanium, and fluoride ionsand to uses thereof as topically effective anticariogenic agents.

It is commonly recognized that the presence of small amounts of fluoridein drinking water (e.g., 1.0 microgram fluoride per milliliter) has apronounced eflect in reducing the incidence of dental caries inpermanent teeth of children consuming such water from birth througheight years of age. Soluble fluoride salts have been introduced intopublic water supplies in a number of communities with good result. Thismedium for providing fluoride is not feasible, however, where drinkingwater is obtained from small, private fluoride-deficient sources such asindividual wells, etc., rather than from fluoridated (naturally orfortified) common public sources. Further, the addition of fluoride tocommon public water sources is not always accepted or permitted nor isit completely eflective. Moreover, much benefit is derived from the useof topical anticariogenic materials even in fluoridated areas.

Topical application of aqueous fluoride solutions by dentists or dentalhygienists provides an excellent measure of protection against caries.Various fluoride compounds have been employed in this manner, includingsodium fluoride, stannous fluoride, and stannous fluorozirconate(SDZIFG), which is the subject of applicants copending United Statespatent application, Stannous Fluorozirconate and Compositions for CariesProphylaxis Containing Same, Ser. No. 291,l73, filed June 27, 1963.Another method of utilizing the antican'ogenic properties of fluoridesalts comprises incorporating such fluoride salts with a compatibleabrasive (such as lava pumice or zirconium silicate) to form aprophylactic paste composition for use by dentists or dental hygienistsin periodic cleaning and polishing of the teeth, as set forth anddescribed in applicants copending United States patent application,Prophylactic Dental Paste Compositions Comprising Zirconium Silicate,Ser. No. 314,602, filed Oct. 8, 1963.

Limitations on the availability and eflectiveness of fluorideprophylaxis by way of water supplies have also led to extensive effortsto incorporate various fluoride salts in oral compositions such asdentifrices, mouthwashes, and the like for use in the home. Again,various fluoride compounds have been employed in this manner, especiallystannous fluoride.

Although effective caries protection has been obtained through the useof the aforementioned fluoride com- 3,441,371 Patented Apr. 29, 1969pounds in compositions adapted for topical application to teeth,occasional side effects have been experienced With certain of the knownanticariogenic agents, particularly certain tin-containing salts. Forthis reason, dental researchers have continued their eflorts to find newcompositions which are not only anticariogenically more effective, butwhich also reduce undesirable side effects.

Accordingly, it is a primary object of the present invention to providenew anticariogenic compounds comprised of zirconium, germanium, andfluorine which exhibit a high level of anticariogenic effectiveness andwhich are relatively non-toxic to living organisms.

It is a related object of the present invention to provide compositionswhich contain the said anticariogenic compounds and which are adaptedfor topical use in preventive dentistry.

A further object is to provide anticariogenic compounds of the characterdescribed which can be used at very high concentrations relative toknown anticariogenic fluoride-containing compounds.

Yet another object of the present invention is to provide an improvedmethod of reducing the solubility of dental enamel which comprises thetopical application thereto of compositions containing the saidanticariogenic compounds.

These and other objects, advantages, and features of the subjectinvention will hereinafter appear, and, for purposes of illustration,but not of limitation, various exemplary embodiments of the subjectinvention are hereinafter described in detail.

In accordance with the subject invention, new salts comprisingzirconium, germanium, and fluoride ions have been discovered.Specifically, these salts are zirconium hexafluorogermanate [Zr(GeP andZirconyl hexafluorogerrnanate [ZrOGeF It has been further found thatthese new compounds are highly effective as anticariogenic agents whenutilized topically (i.e., in local applications to the teeth) eitheralone or in combination with other materials, as hereinafter described.

PREPARATION AND PROPERTIES 4.181 g. (0.025 mole) of anhydrous ZrF and5.23 g. (0.05 mole) of GeO were dissolved in 25.392 ml. of 50 percentaqueous hydrofluoric HF solution, and the Zr(GeF crystals were collectedin accordance with the method above indicated. Zr(GeF synthesized inthis manner was obtained in an 88 percent yield. Theoretical and actualchemical analyses of this product conformed to the values reported inTable I.

TABLE I.-ANALYSES Theoretical (percent) Element Actual (percent)Fluorine Germanium. ZlICODlUJIl Zirconyl hexafluorogermanate [ZrOGeF isa graywhite crystalline compound which melts at a temperature in excessof 310 C. and which has a refractive index of 1.558. ZrOGeF can beprepared in the following manner. One mole of GeO and two moles ofpotassium fluoride [KP] are dissolved in an excess of 50 percent HFsolution. The resulting solution is neutralized with 50 percentpotassium hydroxide [KOH], thereby precipitating potassiumhexafluorogermanate [K GeF which is collected. An equimolar mixture of KGeF and zirconium oxychloride [ZrOCl l is dissolved in a minimal amountof Water, and the resulting solution evaporated. The precipitate, whichis ZrOGeF is collected and dried.

Example II 5.230 g. (0.050 mole) of GeO and 2.905 g. (0.05 mole) of KFwere dissolved in 25.392 ml. of 50 percent TABLE III.-X-RAY DIFFRACIIONDATA Z1'( GeFm ZrO GeF ZrF; GeOzGlex) GeOz(tetra) ZrO Ol2.8H-.O

d I d I d I d I d I d I d I 6. 41 100 6. 88 25 1. 92 40 4. 32 21 3. 118100 12. 8 100 4. 33 8 6. 09 20 1. 91 20 3. 429 100 2. 3999 60 10. 6 273. 97 100 4. 95 6 1. 87 20 2. 496 11 2. 199 15 7. 9 20 3. 85 35 4. 7530 1. 85 20 2. 366 22 2. 106 13 6. 9 63 3. 46 75 3. 87 100 l. 83 20 2.283 13 1. 967 4. 80 17 3. 42 45 3. 64 60 1. 79 3O 2. 159 18 1. 620 50 4.12 27 3. 30 95 3. 44 80 1. 77 1O 2. 018 2 1. 555 17 3. 82 20 3. 21 90 3.27 30 1. 76 6 1 384 8 3. 60 83 2. 92 6 3. 11 20 1. 75 14 3. 24 40 2. 735 3. 04 40 1. 73 10 4 2. 96 7 2. 58 50 3. 02 50 1. 72 6 7 2. 74 7 2. 493 2. 64 2 1. 70 4 3 2. 55 7 2. 43 5 2. 49 6 1. 67 4 13 2. 39 7 2. 37 82. 48 6 1. 65 6 2. 22 13 2. 28 5 2. 47 6 1. 6O 4 2. 2. 25 15 2. 37 4 1.565 10 2. 07 13 2. 23 7 2. 28 4 1. 530 6 2. 00 7 2. 15 8 2. 02 6 1. 51010 1. 91 13 2. 10 20 1. 96 O 1. 480 4 1. 81 13 1. 93 45 1. 94 O 1. 44 1. 71 13 1. 87 100 1, 2 1.85 25 1.57 1. 83 45 1. 51 1 4 1 Evaluated bypaper trace, X-ray ditlraction procedure.

TABLE II.. \NALYSES Element Theoretical (percent) Actual (percent)Fluorine 38. 80 38. 7 Germanium. 24. 71 24. 8 Oxygen 5. 5. 5 Zirconium31. 05 31.0

The presently disclosed zirconiurn-germanium-fiuoride salts have eachbeen characterized according to the conventional Hull-Debye-ScherrerX-ray diffraction powder technique in order to produce a film record.Exposure was made using a standard X-ray diffraction camera (diameter114.6 mm.) for 4.0 hours at 35 kv. and 18 ma. with a copper target and anickel filter. As is known to one skilled in the art, this techniquecauses all chemical compounds to retract X-rays according to a patternspecific for each compound. The X-rays expose a film according to aspecific pattern, which appears on the film as characteristic lines, theinter-planar spacing of which and the relative intensity of which may bemeasured in order to identify the compound. Table III recordsmeasurements obtained from a film record when each of theZirconium-germanium-fluoride salts was treated as described,

ANTICARIOGENIC EFFECTIVENESS The anticariogenic effectiveness of thezirconiumgermanium-fluoride salts may be demonstrated by the dentalcaries experience of rats (standard experimental animals foranticariogenic studies). The effect of various compositions in reducingthe solubility of dental enamel in acid is a reliable indicator ofanticariogenicity. Enamel solubility characteristics of dentalcompositions can be determined by a number of tests well known in theart. The particular test for reduction in tooth enamel solubilitydescribed herein comprises a comparison of acid solubility of a giventooth before and after treatment with a given test composition. The saidcomparison is expressed as ESR, that is, enamel solubility reduction.

Rat tooth ESR is determined in vivo as follows. The teeth of a group ofsuitably selected test rats are given single one-minute topicalapplications with solutions of various fluorides, and the animals aresacrified twenty minutes thereafter. Each mandibular hemijaw is removedand the clinical crowns of each are decalcified in 0.2 N (pH 4) sodiumacetate butter for twenty minutes, and the decalcification solutions areanalysed for phosphorus by a colorimetric method (Fisk and Subbarow, TheColorimetric Determination of Phosphorus, Journal of BiologicalChemistry, 662375, 1925). Phosphorus liberation of the teeth topicallytreated with the various fluoride solutions is compared with that ofteeth similarly treated with nonfluoride containing control solutions,and the result of such comparison is reported as a percentage reductionof enamel solubility (i.e., ESR).

Table IV reports percentage reduction values achieved in the rat toothESR test with topically applied aqueous solutions of thezirconium-germanium-fiuoride salts of the present invention at a 1000ppm. fluoride ion level. The high level of anticariogenic activity ofthe new compounds is clearly evidenced by the percentage reductionvalues shown below.

TAB LE IV pH 01 ESE mean Compound solution percent reduction ZI(GeFa)22.3 70.06 ZrO GeFs 2. 5 70. 83

E S R mean percent reduction Percent conc.

Fluoride compd.

Z1( GeFa) z ZrO GeFs Tables VI-VIII report comparative ESR data achievedwith the new zirconium-germanium-fluoride salts and several knownfluoride-containing anticariogenic agents. In the studies reported inTable VI, the aqueous test solutions were prepared so that each wasequivalent (on a fluoride ion basis) to an 8 percent SnF solution.Likewise, in Table VII the aqueous solutions or slurries were allequivalent to a 24 percent SnF solution, and in Table VIII the solutionsor slurries were all equivalent to a 24 percent SnZrF solution. In allcases the new Zirconium-germanium-fiuoride salts were at least aseffective as the tested known anticariogenic compounds.

TABLE VI E S R mean Percent pH percent Fluoride compd. cone. (natl)reduction 8. 2. 6 24. 4. 29 6. 9 16. 3 3. 95 1. 4 81. 5 5. 0O 1. 5 81. 6SnZrFc. 5. 51 2. 1 26. 5

TABLE VII ESR mean Percent pH percent Fluoride compd. cone. (natl)reduction 24. 00 2. 3 46. 7 12. 86 6. 7 30. 3 11. 86 1. 0 93. 1 15.00 1. 7 84.3 SnZrFa 16. 54 1. 7 81.4

TABLE VIII ES R mean Percent pH percent Fluoride compd. cone. (natl)reduction data illustrating duration of effectivesacrificed twentyminutes after receiving the initial topical treatment. The othersubgroups were sacrificed at the following intervals of time: two andone-half days; five days;

and ten days. The topical solutions were equalized to the fluoridecontent of 8 percent Zr(GeF The hemijaws were prepared and the enamelsolubilities determined as hereinbefore described. It a minimum desiredreduction level of 50 percent is selected, thezirconium-germaniumfluorides would require reapplication only half asOften as SnF or SnZrF TAB LE IX ES R mean percent reduction PercentFluoride compd. conc. 20 min. 2% days 5 days 10 days SnF2 16. 2 59. 954. 8 25. 0 17. 8 SnZrFa. 11. 2 62. 0 58. 9 23. 5 23. 8 ZrO GeF 10.192.1 79. 8 45. 8 52. 0 Zr(GeFs)2. 8 94. 4 80. 5 64.1 63. 8

Table X shows data indicating that significant anticariogeniceffectiveness is achieved even though the duration of the topicalapplication is relatively short. Eight percent aqueous solutions of thecompounds were applied for periods ranging from 15 seconds to severalminutes. The enamel solubilities were determined by the rat tooth ESRtest hereinbefore described.

The new zirconium-germanium-floride salts of the present invention alsohave outstanding utility as antican'ogenic constituents of oralcompositions for caries prophylaxis. In general, such compositions(which include topical solutions, prophylactic paste compositions, anddentifrice preparations) will contain from about 0.1 to about 50% of thezirconium-germanium-fluoride salts of the present invention. Oralcompositions which are designed for relatively frequent use in the home(e.g., dentifrice and mouthwash preparations) typically contain lowerlevels of the salts of the present invention than do the prophylacticpastes or topical solutions. Dentifrice preparations preferably comprisefrom about 0.1 to about 0.5 zirconium-germaniumfluoride salts.Prophylactic paste compositions preferably comprise about 10 to 30% ofthe zirconium-germaniumfluoride salts of the present invention. Topicalsolutions incorporating the zirconium-germanium-fluoride salts of thepresent invention preferably comprise about 0.1 to about 50% of thesalt, and preferably about 40 to 20% of the salts.

Dentifrice compositions containing the zirconium-germanium-fluoridesalts constitute a preferred embodiment of this invention and maycontain the usual dentifrice components, but preferably, ionicallycompatible adjuvants are used. For example, resinous abrasive materialsincluding particulate condensation products of melamine and urea orformaldehyde and the like which do not form insoluble salts withfluoride ion or inactivate zirconium, germanium, and fluoride ions byadsorption can be used to advantage. Other abrasives which have provenpractical in fluoride containing dentifrice compositions and which canbe used herein include zirconium silicate, calcium pyrophosphate,insoluble metaphosphates and alumina. Mixtures of these abrasives canalso be used.

The total amount of abrasive material in dentifrices of this inventioncan range from 0.5% to by weight of the total composition. Preferably,toothpastes contain from 20% to 60% by weight and toothpowders containfrom 60% to 95% by weight.

Toothpastes require a binder substance to impart desired textureproperties. Natural gum binders such as gum tragacanth, gum karaya, gumarabic, etc. and seaweed derivatives such as Irish moss and alginates,and water soluble cellulose derivatives, such as hydroxyethyl-celluloseand sodium carboxylmethyl cellulose can be used for this purpose.Desirably those materials are employed which are most compatible withfluoride ion. Binders which have no ionic groups, such as hydroxyethylcellulose are especially preferred. Improvements in texture can also beattained by including an additional material such as colloidal magnesiumaluminum silicate.

Thickening agents in an amount of from 0.5% to 5.0% by Weight can beused to form a satisfactory toothpaste.

Toothpastes conventionally contain sudsing agents. Suitable sudsingagents include, but are not limited to, Water-soluble alkyl sulfateshaving from 8 to 18 carbon atoms in the alkyl radical, such as sodiumlauryl sulfate, water-soluble salts of sulfonated monoglycerides offatty acids having from 10 to 18 carbon atoms in the alkyl radical suchas sodium coconut monoglyceride snlfonate, salts of fatty acid amides oftaurines such as sodium-N- methyl pa-lmitoyl tauride, and salts of fattyacid esters of isethionic acid.

Sudsing agents can be used in the compositions of this invention in anamount of from about 0.5% to about 5.0% by weight of the totalcomposition.

It is also desirable to include some humectant material in a toothpasteto keep it from hardening. Materials commonly used for this purposeinclude glycerine, sorbitol and other polyhydric alcohols. Thehumectants can comprise up to 35% of the toothpaste composition.

8 data was obtained in the previously described manner. The results ofthese tests are given in Table XI. The sample dentifrices utilized asthe anticariogenic active component mixtures of a fluoride-containingsalt and an activephosphate compound, for example, an ammonium salt of acondensation product of NH and P 010, e.-g.,

commercially available under the trade name Victamide from VictorChemical Company, in the manner set forth and described in applicantscopending United States patent application, Dentifrice Preparation, Ser.No. 402; 920, filed Oct. 9, 1964. As their cleaning and polishingcomponents, the dentifrices utilized a critically defined zirconiumsilicate [ZrSiO in accordance with applicants copending United Statespatent application, Anticariogenic and Anti-Calculus Dentifrice Cleaningand Polishing Agent and Dentifrice Preparations Incorporating Same, Ser.No. 453,515, filed May 5, 1965.

The data reported in Table XI verify the high level of anticariogenicityobtained with dentifrice preparations embodying thezirconium-germanium-fluoride salts of the present invention.

TABLE XI.ANTICARIO GENIG EFFE CTIVENESS F ZIRC ON IUM-GE RMANI UM-FLUORIDE SALTS Constituents, parts by weight Sorbitol Group No. ZrSiOi ZrOGeF Z1(GeFa)z Victamide Water Glycerin 70% aqueous Sudsers Binders 1(control) 2 18 10 10 1. 2 2. 0 18 10 10 1. 2 2. 0 10 18 10 10 1. 2 2. 015 18 10 10 1. 2 2. 0 10 18 10 10 1. 2 2. 0 15 18 10 10 1. 2 2. 0 10 1810 10 1. 2 2. 0 15 18 10 10 1. 2 2. 0 10 18 10 10 1. 2 2. 0 15 18 1010 1. 2 2. 0 10 18 10 1O 1. 2 2. 0 15 18 10 10 1. 2 2. 0

Constitutents, parts by weight ESR data Group No. M-HPO H PO4 Z!(PO3 4ZrP2O Z1' (P04)4 KHC H4O4 Brushing pH N o. of Teeth Mean Red 1 (control)7. 0 10 2 2. 0 4. 0 10 71. 0 3 2. 0 3. 85 9 63. 5 4 2. 0 3. 9 10 66. 35. 2. 0 4. 2 10 62. 2 6- 2. 0 4. 0 9 71. 1 7. 2. 0 4. 2 8 73. 8 8. 2. 04. 1 10 60. 0 9. 2. 0 4. 0 9 68. 7 10 2. 0 4. 0 10 66. 0 11.. 2. 0 3. 910 66. 5 12... 2 0 3. 9 10 63. 1 13 2. 0 4. 0 9 75. 8

with this invention can be seen from the following studies.

A suitable number of rats were divided into thirteen equal groups, andthe teeth of each rat were brushed five times within a three-hour periodwith a sample dentifrice preparation. The rats were sacrificedthereafter, and ESR When incorporated in dentifrice preparations, thenovel zirconium-germanium-fluoride salts of the present invention arecomparable in effectiveness to other known anticariogenic agents (suchas, for example, SnF Table XII records rat ESR data obtained in abrushing study, carried out according to the previously describedprocedure in which dentifrices comprising SnF and Victamide areutilized. The data of Table XII verify the high level of anticariogeniceffectiveness of dentifrice preparations embodying the salts of thepresent invention.

TABLE XIL-ANTICARIO GENIC EFFECTIVENESS OF VARIOUS FLUORIDE CONTAININGDENTIFRICE PREPARATIONS Constituents, parts by weight ESR data Sorbi-Mean Victa- Glyotel Sud- Bind- Brush- No. of percent ZrSiO4 SIlFz ZrOGeFa mide Water erin aqueous sers ers M-HPO3 11 1 04 S111P O KHC H4O4ing pH teeth Red 10 10 10 10 1. 5 2. 3 1. 0 4. 0 10 77. 9 12 5 10 10 101.5 2.3 1.0 4.0 10 72.8 l5 l0 l0 10 1.5 2.3 1. 0 3.95 10 77.3 10 22 l010 1.2 2. 0 l. 0 4. 5 0 70.1 [0 22 l0 10 1.2 2.0 1.0 4.0 10 05. 7 1U 22l0 10 1.2 2. 0 1. 0 5. 0 10 70.4

The following examples provide exemplary dentifrice formulationscomprising the zirconium-germanium-fluoride salts of the presentinvention.

Example III A toothpaste composition is prepared by conventional methodshaving the following composition:

Percent by weight Zirconium hexafiuorogermanate 0.22 Zirconium silicate44.18 Victamide 5.01 Distilled water 14.09 Glycerin 7.59 Sorbital (70%aqueous solution) 9.21 Sodium coconut monoglyceride sulfonate 0.87Sodium lauryl sulfate 0.87 Veegum (magnesium aluminum silicate) 0.33Sodium carboxymethyl cellulose 1.35

Meta-phosphoric acid 11.38

Potassium acid phthalate 2.00 Flavoring agents 1.00 Coloring agents 1.08Saccharin 0.82

When diluted with water and brushed upon the teeth in the conventionalmanner, this composition yields substantial reductions in carriesincidence.

TAB LE XIII Prophylactic paste constituents ESR data percent PolishingWater mean agent Percent Fluoride Percent percent reduction Lava pumice-67. 33. 0 ZrSiO4- 82. 0 16. 0 65. 6 ZrSiO4 76.0 16. 0 87. 4 ZrSiO4 84. 014. 0 60. 2 ZrSiOr. 78.0 14. 0 91. 2 ZrSiO4 55. 0 15. 0 78. 5 Lavapumice- 61. 1 30. 0 66. 8

The anticariogenic effectiveness of the novelzirconiumgermanium-fluoride salts has also been verified in humanclinical studies. A total of approximately 150 children between the agesof 6-15 years were divided in accordance with past dental cariesexperience into three balanced groups. Each member of each groupreceived a thorough dental prophylaxis before the clinical study wasbegun. Each member of each group received treatment with a topicalsolution and was examined after six months. The children in Group Ireceived an 8% solution of Zr(GeF Group II received a 12. 6% solution ofZrOGeF and Group III received a 0.9% NaCl solution. The increments inthe number of decayed, missing, and filled teeth (ADMFT) and theincrements in the number of decayed, missing, and filled surfaces(A-DMFS) were recorded. The percentage reduction in caries incidence wasestablished by comparison with the control group (Group III). Theresults of this study are presented in Table XIV.

TABLE XIV.HUMAN CLINICAL STUDIES No. of

Percent Red. Fluoride C0nc.,

Teeth Surfaces Example IV Another toothpaste composition is prepared asin Example III, but containing zirconyl hexafluorogermanate in place ofzirconium hexafluorogermanate. This composition provides an effectivemeans for caries prophylaxis when used in the conventional manner.

The new zirconium-germanium-fiuoride compounds are useful asanticariogenic constituents when incorporated with a cleaning andpolishing agent (e.g., lava pumice or Zirconium silicate) to form aprophylactic paste adapted for application once or twice a year by adentist or dental hygienist. Preferred prophylactic pastes embodyingzirconium silicate are set forth and described in applicants copendingUnited States patent application entitled Prophylactic Dental PasteCompositions Comprising Zirconium Silicate, Ser. No. 314,602, filed Oct.8, 1963. Table XIII contains representative ESR results obtained throughthe use of various prophylactic paste compositions. A suitable number oftest rats were divided into groups and each group was given a -secondprophylaxis with one of the compositions. Twenty minutes followingtreatment, the animals were sacrificed, and enamel solubilities weredetermined in the usual manner. The data of Table XIII illustrate thehigh level of anticariogenic effectiveness obtained with prophylacticpaste compositions embodying the salts of the present invention.

The results of the human clinical studies, as reported in Table XIV,clearly establish the anticariogenic effectiveness of thezirconiumgermanium-fluorides of the present invention.

As previously noted, the new zirconium-germaniumfiuoride salts of thepresent invention are especially useful when incorporated in oralcompositions for caries prophylaxis.

ANIMAL TOXICITY In addition to exhibiting a high level of anticariogeniceffectiveness, the zirconium-germanium-fluoride salts of the presentinvention are of low toxicity comparing quite favorably in this regardwith other anticariogenic fluorides, as shown by the followingexperimental studies.

The toxicity of the zirconium-germanium-fluoride salts has beendetermined in mice (standard experimental animals for this purpose), andacute toxicity data are shown in Table XV, with corresponding values forNaF included for comparative purposes. The toxicity is expressed interms of an LD which is the lethal dose for 50% of the animals treated.The LD is expressed both in milligrams of fluoride per kilogram of bodyweight and in milligrams of compound per kilogram of body weight. Thedata reveals that the test mice could tolerate significantly greateramounts of exempary zirconium-germanium-fiuoride salts than of sodiumfluoride.

TABLE XV.-ACUTE TOXICITY Rat studies further reveal thatzirconium-germaniumfiuoride salts, when topically applied, do not damagethe gingival tissue of the test animals. Groups of weanling rats weregiven topical applications of various fluoride compounds, and thegingival tissues were examined after 24 hours. The results indicate thatthe exemplary zirconium-germanium-fluoride salts are comparable orsuperior to known fluorides (e.g., NaF, SnF or SnZrF The particularzirconium-germanium-fluoride salts set forth and described hereinbeforeare believed to 'be representative of a class of theoreticallyobtainable zirconiumgermanium-fluoride salts. Thus, it is believed thatother zirconium-germanium-fluoride salts may be prepared and such othersalts would be expected to exhibit the same anticariogenic utility asthe specific salts disclosed herein.

While the present invention has been described herein with reference tocertain exemplary embodiments thereof, it should be understood thatvarious changes, modifications, and alterations may be effected in thematerials utilized, in the proportions of materials, and in the mannersof formulation without departing from the spirit and the scope of thepresent invention, as defined in the appended claims.

What is claimed is:

1. An anticariogenic salt comprising a member selected from the groupconsisting of zirconium hexafluorogermanate [Zr(GeF and zirconylhexafluorogermanate [ZrOGeF 2. An anticariogenic salt, as claimed inclaim 1, wherein the member is zirconium hexafiuorogermanate 3. Ananticariogenic salt, as claimed in claim 1 wherein the member iszirconyl hexafluorogermanate [ZrOGeF References Cited Gebala et al.:Journal of Inorganic and Nuclear Chemistry, vol. 29, September 1967, pp.2301-2305.

Johnson: Chemical Reviews, vol. 51, 1952, p. 462 of Interest.

Ryss: The Chemistry of Fluorine and Its Inorganic Compounds, Part 1, US.Atomic Energy Commission Report AECtr-3927 (Pt. 1), 1960, Oak Ridge,Tenn., pp. 346-349.

HERBERT T. CARTER, Primary Examiner.

U.S. c1. X.R. 23-88; 16793

